Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coxsackie B1-6 virus IgM responses were detected by an enzyme-linked immunosorbent assay (ELISA) in 11 of 28 (39%) children aged 3-14 years in whom insulin-dependent (juvenile onset; type I) diabetes mellitus (IDDM) developed in 1982. 5 patients had a homotypic response to Coxsackie B4 and 1 had a homotypic response to B5. A serum sample had been obtained from each patient 2 to 16 weeks after onset of IDDM symptoms. Islet-cell cytoplasmic antibodies (IgG) and complement fixing islet cell antibodies were detected in 15 of 18 sera tested, but only 6 of these sera were positive for Coxsackie-B-virus-specific IgM which suggests that Coxsackie-B-virus and islet-cell antibodies are not cross-reactive. Coxsackie-B-virus-specific IgM responses were present in only 16 of 290 (5.5%) age-matched non-diabetic London children whose sera were also collected during 1982. Sera from children with virologically confirmed Coxsackie-B-virus infections showed that development of homotypic or heterotypic Coxsackie B1-6 responses was age-related. 29 of 36 (81%) children aged 6 months to 4 years had a homotypic response, whereas 44 of 57 (77%) persons aged 15 years had heterotypic responses. Mothers of 2 children with Coxsackie-B-virus-induced neonatal myocarditis had Coxsackie-B-virus-specific IgM responses directed against serotypes 3 and 4, whereas their infants had a response to Coxsackie B2 virus alone.
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PMID:Coxsackie-B-virus-specific IgM responses in children with insulin-dependent (juvenile-onset; type I) diabetes mellitus. 613 78

We report a case of diabetic ketoacidosis (DKA) complicated by acute myocarditis, which was confirmed by cardiac biopsy. A 26-year-old man was hospitalized with severe DKA. On admission, nonspecific ST-T change was noted on the electrocardiogram (ECG). The patient's levels of creatine phosphokinase (CPK) and glutamic oxaloacetic transaminase were slightly elevated, but he did not complain of chest discomfort or symptoms of heart disease. On the first day after admission, ST-T elevation was noted on ECG during treatment of DKA. By cardiac angiography and cardiac biopsy, coronary heart disease was ruled out and postmyocarditic change was histologically confirmed. An episode of upper respiratory viral infection before the onset of acute diabetes suggested that the patient suffered from viral-induced myocarditis and consequent development of IDDM. This possibility was confirmed by the clinical course of ECG change, with elevated CPK and lactate dehydrogenase and a slightly elevated antibody titer for echovirus.
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PMID:A case of myocarditis associated with IDDM. 872 64

Autoimmune diseases remain one of the mysteries that perplex immunologists. What makes the immune system, which has evolved to protect an organism from foreign invaders, turn on the organism itself? A popular answer to this question involves the lymphoid network's primordial function: autoimmunity is a by-product of the immune response to microbial infection. For decades there have been tantalizing associations between infectious agents and autoimmunity: beta-hemolytic streptococci and rheumatic fever; B3 Coxsackieviruses and myocarditis; Trypanosoma cruzi and Chagas' disease; diverse viruses and multiple sclerosis; Borrelia burgdorfii and Lyme arthritis; and B4 Coxsackievirus, cytomegalovirus or rubella and type 1 diabetes, to name the most frequently cited examples. In addition, animal models have provided direct evidence that infection with a particular microbe can incite a particular autoimmune disease. Nonetheless, many of the associations appear less than convincing and, even for those that seem to be on solid footing, there is no real understanding of the underlying mechanism(s).
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PMID:Autoimmunity provoked by infection: how good is the case for T cell epitope mimicry? 1152 89

Idiopathic dilated cardiomyopathy (IDC) is one of the major causes of death in humans and has been linked to Coxsackievirus B (CVB) infection. The aim of this study was to analyze phenotypes of heart-infiltrating immune cells in patients suffering from myocarditis and IDC associated with CVB infections. We found that the myocardium of these patients was infiltrated by CD4(+) and CD8(+) T lymphocytes as well as macrophages. Evidence of CVB3/4 infections was also found. In the majority of patients, the T-cell receptor repertoire (TCR) of the infiltrating lymphocytes was restricted, with a polyclonal expansion of the Vbeta7 gene family. We also found that human leukocyte antigen (HLA) class II alleles associated with susceptibility to type 1 diabetes (HLA-DR4 and HLA-DQA1*04/05/06 alleles) were remarkably infrequent in IDC patients (p < 0.005), thus suggesting that they might confer protection against IDC. Finally, mRNA for interleukin-1beta, interferon-gamma, and tumor necrosis factor-alpha was detected in the cardiac specimens, although at a lower level compared with specimens from hearts without signs of viral infections. We conclude that CVB infection of the human myocardium is associated with a selective, yet polyclonal activation of different T-cell subsets in genetically susceptible individuals. This immune response may play a critical role in modulating disease progression after viral infections.
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PMID:Expansion of specific alphabeta+ T-cell subsets in the myocardium of patients with myocarditis and idiopathic dilated cardiomyopathy associated with Coxsackievirus B infection. 1255 22

Group B coxsackieviruses (CVB) cause numerous diseases, including myocarditis, pancreatitis, aseptic meningitis and possibly type 1 diabetes. To date, infectious cDNA copies of CVB type 3 (CVB3) genomes have all been derived from pathogenic virus strains. An infectious cDNA copy of the well-characterized, non-pathogenic CVB3 strain GA genome was cloned in order to facilitate mapping of the CVB genes that influence expression of a virulence phenotype. Comparison of the sequence of the parental CVB3/GA population, derived by direct RT-PCR-mediated sequence analysis, to that of the infectious CVB3/GA progeny genome demonstrated that an authentic copy was cloned; numerous differences were observed in coding and non-coding sequences relative to other CVB3 strains. Progeny CVB3/GA replicated similarly to the parental strain in three different cell cultures and was avirulent when inoculated into mice, causing neither pancreatitis nor myocarditis. Inoculation of mice with CVB3/GA protected mice completely against myocarditis and pancreatitis induced by cardiovirulent CVB3 challenge. The secondary structure predicted for the CVB3/GA domain II, a region within the 5' non-translated region that is implicated as a key site affecting the expression of a cardiovirulent phenotype, differs from those predicted for cardiovirulent and pancreovirulent CVB3 strains. This is the first report characterizing a cloned CVB3 genome from an avirulent strain.
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PMID:Characterization of an infectious cDNA copy of the genome of a naturally occurring, avirulent coxsackievirus B3 clinical isolate. 1560 47

The autoimmune polyglandular syndrome (APS) is characterized by a variable coexistence of several autoimmune diseases, affecting predominantly endocrine glands. In general two types of APS are distinguished. Type 1 APS is an autosomal recessive disorder often leading to insufficiency of the adrenal cortex, the parathyroid glands, and/or the gonads. This type of APS often affects the skin in form of chronic mucocutaneous candidiasis and ectodermal dystrophies (vitiligo, alopecia, keratopathy, dystrophy of dental enamel and nails). The second form of APS is a polygenic disease which usually involves the adrenal gland, the thyroid and the pancreatic beta-cells. In rare cases APS type 2 is associated with myasthenia gravis, autoimmune thrombocytopenic purpura, Sjogren's syndrome or rheumatoid arthritis. Here we describe a case of APS with the unusual combination of type 1 diabetes, secondary adrenocortical insufficiency, growth hormone deficiency, and primary hypothyroidism associated with lethal idiopathic giant cell myocarditis. The combination of APS and idiopathic giant cell myocarditis which is a rare, frequently fatal autoimmune disorder of myocardium affecting most commonly young individuals has not been reported so far.
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PMID:Autoimmune polyglandular syndrome associated with idiopathic giant cell myocarditis. 1592 18

Human enterovirus (HEV) infections can be asymptomatic or cause only mild illness; recent evidence may implicate HEV infection in type 1 diabetes mellitus and myocarditis. Here, we report the molecular characterization of HEV obtained in serial monthly collections from healthy Norwegian infants. A total of 1,255 fecal samples were collected from 113 healthy infants beginning at age 3 months and continuing to 28 months. The samples were analyzed for HEV nucleic acid by real-time PCR. Fifty-eight children (51.3%) had HEV infections. One hundred forty-five positive samples were typed directly by nucleotide sequencing of the VP1 region. HEV-A was detected most frequently, with an overall prevalence of 6.8%. HEV-B was present in 4.8% of the samples and HEV-C in only 0.2% of the samples. No poliovirus or HEV-D group viruses were detected. Twenty-two different serotypes were detected in the study period: the most common were EV71 (14.5%), CAV6 (10.5%), CAV4 (8.9%), E18 (8.9%), and CBV3 (7.3%). These findings suggest that the prevalence of HEV infections in general, and HEV-A infections in particular, has been underestimated in epidemiological studies based on virus culture.
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PMID:High prevalence of human enterovirus a infections in natural circulation of human enteroviruses. 1694 51

Coxsackie B viruses (CVB) and Echoviruses (EV) form a single species; Human enterovirus B (HeV-B), within the genus Enterovirus. Although HeV-B infections are usually mild or asymptomatic, they can cause serious acute illnesses. In addition, HeV-B infections have been associated with chronic immune disorders, such as type 1 diabetes mellitus and chronic myocarditis/dilated cardiomyopathy. It has therefore been suggested that these viruses may trigger an autoimmune process. Here, we demonstrate that human dendritic cells (DCs), which play an essential role in orchestration of the immune response, are productively infected by EV, but not CVB strains, in vitro. Infection does not result in DC activation or the induction of antiviral immune responses. Instead, EV infection rapidly impedes Toll-like receptor-mediated production of cytokines and upregulation of maturation markers, and ultimately causes loss of DC viability. These results describe for the first time the effect of EV on the function and viability of human DCs and suggest that infection of DCs in vivo can impede regulation of immune responses.
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PMID:Echovirus infection causes rapid loss-of-function and cell death in human dendritic cells. 1729 95

The immune system has evolved to protect the host from microbial infection; nevertheless, a breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide. Although the etiology is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe. Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models. Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells. Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases.
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PMID:Curcumin and autoimmune disease. 1756 23

Cardioviruses cause enteric infections in mice and rats which when disseminated have been associated with myocarditis, type 1 diabetes, encephalitis, and multiple sclerosis-like symptoms. Cardioviruses have also been detected at lower frequencies in other mammals. The Cardiovirus genus within the Picornaviridae family is currently made up of two viral species, Theilovirus and Encephalomyocarditis virus. Until recently, only a single strain of cardioviruses (Vilyuisk virus within the Theilovirus species) associated with a geographically restricted and prevalent encephalitis-like condition had been reported to occur in humans. A second theilovirus-related cardiovirus (Saffold virus [SAFV]) was reported in 2007 and subsequently found in respiratory secretions from children with respiratory problems and in stools of both healthy and diarrheic children. Using viral metagenomics, we identified RNA fragments related to SAFV in the stools of Pakistani and Afghani children with nonpolio acute flaccid paralysis (AFP). We sequenced three near-full-length genomes, showing the presence of divergent strains of SAFV and preliminary evidence of a distant recombination event between the ancestors of the Theiler-like viruses of rats and those of human SAFV. Further VP1 sequencing showed the presence of five new SAFV genotypes, doubling the reported genetic diversity of human and animal theiloviruses combined. Both AFP patients and healthy children in Pakistan were found to be excreting SAFV at high frequencies of 9 and 12%, respectively. Further studies are needed to examine the roles of these highly common and diverse SAFV genotypes in nonpolio AFP and other human diseases.
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PMID:Cardioviruses are genetically diverse and cause common enteric infections in South Asian children. 1919 86


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